Yada Toyotaka, Kaji Shuichiro, Akasaka Takashi, Mochizuki Seiichi, Ogasawara Yasuo, Tanemoto Kazuo, Yoshida Kiyoshi, Kajiya Fumihiko
Department of Medical Engineering and Systems Cardiology, Kawasaki Medical School, Kurashiki, Japan.
Clin Hemorheol Microcirc. 2007;37(3):269-76.
The relationship among the nitric oxide synthase (NOS) inhibitor [asymmetric dimethylarginine (ADMA)], NOS cofactor [tetrahydrobiopterin (BH(4))], and superoxide anion in the patients with acute myocardial infarction (AMI) is still unknown. This study sought to assess the NOS inhibitor and cofactor with oxidative stress in AMI patients (n=9) during initial administration and 4 weeks after medical treatments. We measured plasma NOS inhibitor and cofactor (ADMA and BH(4)) by HPLC and plasma oxidized-LDL by ELISA. Blood samples from age-matched healthy volunteers (n=9) were taken for comparison. In AMI, plasma ADMA, oxidized-BH(4) (BH(2)+biopterin) and oxidized-LDL significantly increased (P<0.0001, P<0.01 and P<0.05 vs. healthy volunteers) and plasma BH(4), plasma nitrate and L-arginine/ADMA significantly decreased compared with healthy volunteers (P<0.0001, P<0.05 and P<0.005 vs. healthy volunteers). Medical treatments improved plasma ADMA, nitrate, BH(4) and oxidized-LDL. In conclusion, ADMA increased, and NO and BH(4) decreased with oxidative stress in AMI, and these mediators improved in AMI patients with medical treatments. These findings indicated that inhibition of NOS with oxidative stress plays a crucial role in endothelial dysfunction in patients with AMI.
急性心肌梗死(AMI)患者中一氧化氮合酶(NOS)抑制剂[不对称二甲基精氨酸(ADMA)]、NOS辅因子[四氢生物蝶呤(BH(4))]与超氧阴离子之间的关系尚不清楚。本研究旨在评估AMI患者(n = 9)在初始给药时及药物治疗4周后,NOS抑制剂和辅因子与氧化应激的关系。我们通过高效液相色谱法测定血浆NOS抑制剂和辅因子(ADMA和BH(4)),并通过酶联免疫吸附测定法测定血浆氧化型低密度脂蛋白。采集年龄匹配的健康志愿者(n = 9)的血样作为对照。在AMI患者中,血浆ADMA、氧化型BH(4)(BH(2)+生物蝶呤)和氧化型低密度脂蛋白显著升高(与健康志愿者相比,P<0.0001、P<0.01和P<0.05),与健康志愿者相比,血浆BH(4)、血浆硝酸盐和L-精氨酸/ADMA显著降低(与健康志愿者相比,P<0.0001、P<0.05和P<0.005)。药物治疗改善了血浆ADMA、硝酸盐、BH(4)和氧化型低密度脂蛋白。总之,在AMI中,ADMA升高,NO和BH(4)随氧化应激降低,且这些介质在接受药物治疗的AMI患者中有所改善。这些发现表明,氧化应激对NOS的抑制在AMI患者内皮功能障碍中起关键作用。